生长分化因子15对骨髓间充质干细胞增殖及基因表达的影响

Abstract

Abstract: Objective To investigate the regulatoty effect of GDF15 on the proliferation and gene expression of BMSCs and its mechanism. Methods The BMSCs were isolated and cultured from rat long bones. The proliferation and cell cycle of BMSCs cultured with different concentrations of recombinant GDF15 proteins were tested by Cell Counting Kit8 and flow cytometry respectively. The mRNA levels of ALP, RunX2, COL1, VEGF, bFGF and HIF1α in BMSCs under induction of GDF15 were detected by real time PCR. Results Under normoxia condition, GDF15 promoted proliferation, cell cycle progress and mRNA level of VEGF in BMSCs dosedependently, and 50 μg/L was the optimum concentration. Conclusion GDF15 promotes proliferation and VEGF gene expression in BMSCs in short time, but its mechanism still needs further study.

Key words: growth differentiation factor 15, bone marrowderived mesenchymal stem cells, cell proliferation

CLC Number:

R349.51

References

[1]Gothard D, Smith EL, Kanczler JM, 〖WTBX〗et al.Tissue engineered bone using select growth factors: A comprehensive review of animal studies and clinical translation studies in man[J].Eur Cell Mater, 2014, 28(6):166-207
[2]Lappalainen OP, Karhula S, Haapea M, 〖WTBX〗et al.Bone healing in rabbit calvarial criticalsized defects filled with stem cells and growth factors combined with granular or solid scaffolds[J].Childs Nerv Syst, 2016, 32(4):681-688
[3]Urakawa N, Utsunomiya S, Nishio M, 〖WTBX〗et al.GDF15 derived from both tumorassociated macrophages and esophageal squamous cell carcinomas contributes to tumor progression via Akt and Erk pathways[J].Lab Invest, 2015, 95(5):491-503
[4]Novosel EC, Kleinhans C, Kluger PJ.Vascularization is the key challenge in tissue engineering[J].Adv Drug Deliv Rev, 2011, 63(45):300-311
[5]JP3〗Martinez CH, Freeman CM, Nelson JD, 〖WTBX〗et al.GDF15 plasma levels in chronic obstructive pulmonary disease are associated with subclinical coronary artery disease[J].Respir Res, 2017, 18(1):42-
[6] 〖JP〗Verhamme FM, Seys LJ, De Smet EG, 〖WTBX〗et al .Elevated GDF15 contributes to pulmonary inflammation upon cigarette smoke exposure［J/OL］. Mucosal Immunol, （2017-02-01）［2017-03-01］. doi: 10.1038/mi.2017.3.〖JP〗
[7]Pavo N, Wurm R, Neuhold S, 〖WTBX〗et al.GDF15 is associated with cancer incidence in patients with type 2 diabetes[J].Clin Chem, 2016, 62(12):1612-1620
[8]Weide B, Schfer T, Martens A, 〖WTBX〗et al.High GDF15 serum levels independently correlate with poorer overall survival of patients with tumorfree stage Ⅲ and unresectable stage Ⅳ melanoma[J].J Invest Dermatol, 2016, 136(12):2444-2452
[9]Song H, Yin D, Liu Z.GDF15 promotes angiogenesis through modulating p53HIF1α signaling pathway in hypoxic human umbilical vein endothelial cells[J].Mol Biol Rep, 2012, 39(4):4017-4022
[10]Jin YJ, Lee JH, Kim YM, 〖WTBX〗et al.Macrophage inhibitory cytokine1 stimulates proliferation of human umbilical vein endothelial cells by upregulating cyclins D1 and E through the PI3KAkt,ERK,and JNKdependent AP1 and E2F activation signaling pathways[J].Cell Signal, 2012, 24(8):1485-1495
[11]Tanrkulu O, Saryldz MA, BatmazI〖DD-*2〗?〖DD〗, 〖WTBX〗et al.Serum GDF15 level 〖JP3〗in rheumatoid arthritis: relationship with disease activity,and subclinical atherosclerosis[J].Acta Reumatol Port, 2017, 42(1):66-72
[12]Teunissen CE, DurieuxLu S, Blankenstein MA, 〖WTBX〗et al.The inflammatory marker GDF15 is not independently associated with latelife depression[J].J Psychosom Res, 2016, 83(4):46-49
[13]Kempf T, Eden M, Strelau J, 〖WTBX〗et al.The transforming growth factorbeta superfamily member growthdifferentiation factor15 protects the heart from ischemiareperfusion injury[J].Circ Res, 2006, 98(3):351-360
[14]Kempf T, von HS, Peter T, 〖WTBX〗et al.Prognostic utility of growth differentiation factor15 in patients with chronic heart failure[J].J Am Coll Cardiol, 2007, 50(11):1054-1060
[15]Lukaszyk E, Lukaszyk M, KocZorawska E, 〖WTBX〗et al.GDF15,iron,and inflammation in early chronic kidney disease among elderly patients[J].Int Urol Nephrol, 2016, 48(6):839-844
[16]Wang X, Chen LL, Zhang Q.Increased serum level of growth differentiation factor 15 (GDF15) is associated with coronary artery disease[J].Cardiovasc Ther, 2016, 34(3):138-143
[17]JP2〗Markel TA, Wang Y, Herrmann JL, 〖WTBX〗et al.VEGF is critical for stem cellmediated cardioprotection and a crucial paracrine factor for defining the age threshold in adult and neonatal stem cell function[J].Am J Physiol Heart Circ Physiol, 2008, 295(6):H2308-2314
[18]Zhang W, Zhu C, Wu Y, 〖WTBX〗et al.VEGF and BMP2 promote bone regeneration by facilitating bone marrow stem cell homing and differentiation[J].Eur Cell Mater, 2014, 27(3):1-11
[19]Heger J, Schiegnitz E, von Waldthausen D, 〖WTBX〗et al.Growth differentiation factor 15 acts antiapoptotic and prohypertrophic in adult cardiomyocytes[J].J Cell Physiol, 2010, 224(1):120-126
[20]Derynck R, Zhang YE.Smaddependent and Smadindependent pathways in TGFbeta family signalling[J].Nature, 2003, 425(6958):577-584
[21]Ago T, Sadoshima J.GDF15,a cardioprotective TGFbeta superfamily protein[J].Circ Res, 2006, 98(3):294-297
[22]Subramaniam S, Strelau J, Unsicker K.Growth differentiation factor15 prevents low potassiuminduced cell death of cerebellar granule neurons by differential regulation of Akt and ERK pathways[J].J Biol Chem, 2003, 278(11):8904-8912
[23]JP3〗Mimeault M, Johansson SL, Batra SK.Marked improvement of cytotoxic effects induced by docetaxel on highly metastatic and androgenindependent prostate cancer cells by downregulating macrophage inhibitory cytokine1[J].Br J Cancer, 2013, 108(5):1079-1091

Effect of the growth differentiation factor 15 on rat bone marrowderived mesenchymal stem cell proliferation and gene expression

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 4

Recommended Articles

Metrics

Comments

[1]	. The protective effects of hyaluronic acid against nicotine in human periodontal ligament fibroblasts [J]. , 2018, 38(4): 314-319.
[2]	. Advance on the role of GDF15 in the angiogenesis and bone metabolism [J]. , 2016, 36(5): 453-457.
[3]	. MicroRNA27b inhibits cell proliferation of oral squamous cell carcinoma through targeting FZD7 [J]. , 2016, 36(3): 200-205.
[4]	. Study on effect of Chloride channel blocker NPPB on the proliferation and differentiation of chicken mandibular mesenchymal cells [J]. , 2015, 35(6): 438-441.